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1.
Article in English | WPRIM | ID: wpr-937697

ABSTRACT

Background and Objectives@#Although human-induced pluripotent stem cells (hiPSC) can be efficiently differentiated into cardiomyocytes (CMs), the heterogeneity of the hiPSC-CMs hampers their applications in research and regenerative medicine. Retinoic acid (RA)-mediated signaling pathway has been proved indispensable in cardiac development and differentiation of hiPSC toward atrial CMs. This study was aimed to test whether RA signaling pathway can be manipulated to direct the differentiation into sinoatrial node (SAN) CMs. @*Methods@#and Results: Using the well-characterized GiWi protocol that cardiomyocytes are generated from hiPSC via temporal modulation of Wnt signaling pathway by small molecules, RA signaling pathway was manipulated during the differentiation of hiPSC-CMs on day 5 post-differentiation, a crucial time point equivalent to the transition from cardiac mesoderm to cardiac progenitor cells in cardiac development. The resultant CMs were characterized at mRNA, protein and electrophysiology levels by a combination of qPCR, immunofluorescence, flow cytometry, and whole-cell patch clamp. The results showed that activation of the RA signaling pathway biased the differentiation of atrial CMs, whereas inhibition of the signaling pathway biased the differentiation of sinoatrial node-like cells (SANLCs). @*Conclusions@#Our study not only provides a novel and simple strategy to enrich SANLCs but also improves our under-standing of the importance of RA signaling in the differentiation of hiPSC-CMs.

2.
Article in Chinese | WPRIM | ID: wpr-936287

ABSTRACT

OBJECTIVE@#To clarify the functional effects of differential expression of ring finger and tryptophan-aspartic acid 2 (RFWD2) on dendritic development and formation of dendritic spines in cerebral cortex neurons of mice.@*METHODS@#Immunofluorescent staining was used to identify the location and global expression profile of RFWD2 in mouse brain and determine the co-localization of RFWD2 with the synaptic proteins in the cortical neurons. We also examined the effects of RFWD2 over-expression (RFWD2-Myc) and RFWD2 knockdown (RFWD2-shRNA) on dendritic development, dendritic spine formation and synaptic function in cultured cortical neurons.@*RESULTS@#RFWD2 is highly expressed in the cerebral cortex and hippocampus of mice, and its expression level was positively correlated with the development of cerebral cortex neurons and dendrites. RFWD2 expression was detected on the presynaptic membrane and postsynaptic membrane of the neurons, and its expression levels were positively correlated with the length, number of branches and complexity of the dendrites. In cultured cortical neurons, RFWD2 overexpression significantly lowered the expressions of the synaptic proteins synaptophysin (P < 0.01) and postsynapic density protein 95 (P < 0.01), while RFWD2 knockdown significantly increased their expressions (both P < 0.05). Compared with the control and RFWD2-overexpressing cells, the neurons with RFWD2 knockdown showed significantly reduced number of dendritic spines (both P < 0.05).@*CONCLUSION@#RFWD2 can regulate the expression of the synaptic proteins, the development of the dendrites, the formation of the dendritic spines and synaptic function in mouse cerebral cortex neurons through ubiquitination of Pea3 family members and c-Jun, which may serve as potential treatment targets for neurological diseases.


Subject(s)
Animals , Aspartic Acid/metabolism , Cerebral Cortex , Dendritic Spines/metabolism , Mice , Neurons/metabolism , Synapses , Tryptophan/metabolism
3.
Article in Chinese | WPRIM | ID: wpr-936211

ABSTRACT

Objective: To propose total posterior nasal neurectomy with transection of sphenopalatine neurovascular bundle from anatomy for the treatment of allergic rhinitis, and to explore its clinical application. Methods: Two fresh cadaveric heads (4 sides) were dissected through endoscopic transnasal middle meatus approach at Otorhinolaryngology Anatomy Laboratory of China-Japan Friendship Hospital. The structures of the craniofacial bone related to the surgical approach were observed. Twelve patients with allergic rhinitis who treated in Department of Otorhinolaryngology, China-Japan Friendship Hospital from Feb. 1 2019 to Jun. 10 2021 were selected. All the patients were treated by posterior nasal neurotomy with the technique of complete transection of sphenopalatine neurovascular bundle and followed up for 1 year after sugery. During the follow-up, 2 patients were lost. The other 10 patients included 4 males and 6 females, aging from 29 to 69 years. Visual Analogue Scale (VAS) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) were used to evaluate the effect of the surgery. SPSS 25.0 software was used for statistical analysis. Results: Important anatomic landmarks of transnasal middle meatus approach were obtained during anatomy, such as ethmoid crest, sphenopalatine foramen/notch, palatine orbital process and sphenopalatine process. The postoperative VAS scores of nose, eye, pharynx, ear and whole body and total VAS scores were significantly lower than those before operation, with statistically significant difference (nose 2.50±1.70 vs 6.47±2.17, eyes 1.15±0.89 vs 3.60±2.57, pharynx 1.30±1.36 vs 4.25±3.64, ear 1.10±1.03 vs 2.67±2.00, whole body 1.08±1.24 vs 3.60±1.17, total 7.13±4.31 vs 20.58±9.05, all P<0.05). The postoperative RQLQ scores of sleep, nose, eyes, practical problems, emotion, activity and the total RQLQ scores of patients were significantly lower than those before operation, with statistically significant difference (sleep 0.80±0.69 vs 2.93±1.33, nose 1.38±1.18 vs 3.93±1.50, eyes 0.58±0.66 vs 1.80±1.25, practical problems 1.10±1.22 vs 3.03±1.84, emotion 1.00±1.81 vs 2.58±2.00, activity 2.77±2.93 vs 6.00±1.85, total 8.99±8.92 vs 22.42±8.69, all P<0.05). There was no significant difference in preoperative and postoperative scores of non-nasal/ocular symptoms (1.37±1.60 vs 2.16±1.12, P=0.166). There was no other complication except 2 cases with short-term postoperative numbness. Conclusions: Total posterior nasal neurectomy with transection of sphenopalatine neurovascular bundle is a safe, effective and feasible method for the treatment of intractable allergic rhinitis, and its long-term efficacy needs further observation.


Subject(s)
Denervation/methods , Female , Humans , Male , Nose/surgery , Quality of Life , Rhinitis, Allergic/surgery , Treatment Outcome
4.
Article in Chinese | WPRIM | ID: wpr-936208

ABSTRACT

Objective: To guide the patients with vertigo who are suitable for vestibular rehabilitation therapy (VRT), and to evaluate the curative effect through a remote guidance platform based on mobile internet. Methods: Adult outpatients, who were diagnosed as vestibular disorders and required VRT, were selected and conducted baseline evaluation and formulated vestibular rehabilitation plan according to their symptoms, diagnosis and vestibular function examination results. These patients downloaded and installed the mobile internet remote guidance platform app for VRT, and then registered and uploaded medical records. According to the VRT plan formulated by clinicians for patients, the platform launched corresponding exercise guidance videos to guide them to complete 4-week VRT exercise at home. Before and after VRT, the patients were scored with Visual Analogue Scale (VAS), Activities-specific Balance Confidence (ABC), Dizziness Handicap Inventory (DHI) and Self-rating Anxiety Scale (SAS). The rehabilitation effects were statistically analyzed by SigmaStat 4.0 software. Results: From October 2019 to October 2021, 233 patients with vertigo completed the registration of vestibular rehabilitation guidance platform, of whom 187 patients insisted on 4-week rehabilitation training and completed the scale evaluation. Among 187 patients, 65 were male and 122 were female; Age was (49.8±16.0) years; The medical history ranged from one to 192 months, with a median of eight months. Compared with that before rehabilitation exercise, the subjective feeling of vertigo in 170 patients was improved, and the overall effective rate was 90.9% (170/187). The subjective symptoms of vertigo were basically improved after rehabilitation training in patients with unilateral vestibular dysfunction, vestibular neuritis, sudden deafness with vertigo, Hunt syndrome and acoustic neuroma. There were significant differences in ABC, DHI and SAS scores before and after VRT (P<0.05). Of those patients with Meniere's disease in the intermittent period and the patients with Meniere's disease who underwent surgical treatment, more than 90% of their subjective symptoms of vertigo or dizziness improved after VRT, and there were significant differences in the scores of ABC, DHI and SAS before and after VRT exercise (P<0.05). In patients with vestibular migraine, 36.7% (11/30) had no improvement or even aggravation of subjective symptoms of vertigo after VRT, however, the DHI score after rehabilitation exercise was lower than that before exercise, and the difference was statistically significant (P<0.05). In patients with bilateral vestibular dysfunction, although most (6/8) subjective symptom scores were improved compared with those before exercise, there was no significant difference in ABC, DHI and SAS scores before and after rehabilitation (P>0.05). Conclusion: VRT with the help of vestibular rehabilitation mobile internet remote guidance platform can effectively improve the subjective symptoms of vertigo, balance ability and anxiety in patients with unilateral vestibular lesions.


Subject(s)
Adult , Dizziness , Female , Humans , Internet , Male , Postural Balance , Vertigo , Vestibular Neuronitis/diagnosis
5.
Frontiers of Medicine ; (4): 263-275, 2022.
Article in English | WPRIM | ID: wpr-929205

ABSTRACT

Emerging evidence indicates that the gut microbiome contributes to the host immune response to infectious diseases. Here, to explore the role of the gut microbiome in the host immune responses in COVID-19, we conducted shotgun metagenomic sequencing and immune profiling of 14 severe/critical and 24 mild/moderate COVID-19 cases as well as 31 healthy control samples. We found that the diversity of the gut microbiome was reduced in severe/critical COVID-19 cases compared to mild/moderate ones. We identified the abundance of some gut microbes altered post-SARS-CoV-2 infection and related to disease severity, such as Enterococcus faecium, Coprococcus comes, Roseburia intestinalis, Akkermansia muciniphila, Bacteroides cellulosilyticus and Blautia obeum. We further analyzed the correlation between the abundance of gut microbes and host responses, and obtained a correlation map between clinical features of COVID-19 and 16 severity-related gut microbe, including Coprococcus comes that was positively correlated with CD3+/CD4+/CD8+ lymphocyte counts. In addition, an integrative analysis of gut microbiome and the transcriptome of peripheral blood mononuclear cells (PBMCs) showed that genes related to viral transcription and apoptosis were up-regulated in Coprococcus comes low samples. Moreover, a number of metabolic pathways in gut microbes were also found to be differentially enriched in severe/critical or mild/moderate COVID-19 cases, including the superpathways of polyamine biosynthesis II and sulfur oxidation that were suppressed in severe/critical COVID-19. Together, our study highlighted a potential regulatory role of severity related gut microbes in the immune response of host.


Subject(s)
COVID-19 , Clostridiales , Gastrointestinal Microbiome , Humans , Immunity , Leukocytes, Mononuclear , SARS-CoV-2
6.
Frontiers of Medicine ; (4): 93-101, 2022.
Article in English | WPRIM | ID: wpr-929197

ABSTRACT

Inducing durable and effective immunity against severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) via vaccination is essential to combat the current pandemic of coronavirus disease 2019 (COVID-19). It has been noticed that the strength of anti-COVID-19 vaccination-induced immunity fades over time, which calls for an additional vaccination regime, as known as booster immunization, to restore immunity among previously vaccinated populations. Here we report a pilot open-label trial of a third dose of BBIBP-CorV, an inactivated SARS-CoV-2 vaccine (Vero cell), on 136 participants aged between 18 to 63 years. Safety and immunogenicity in terms of neutralizing antibody titers and cytokine/chemokine responses were analyzed as the main endpoint until day 28. While systemic reactogenicity was either absent or mild, SARS-CoV-2-specific neutralizing antibody titers rapidly arose in all participants within 4 weeks, surpassing the peak antibody titers elicited by the initial two-dose immunization regime. Broad increases of cellular immunity-associated cytokines and chemokines were also detected in the majority of participants after the third vaccination. Furthermore, in an exploratory study, a newly developed recombinant protein vaccine, NVSI-06-08 (CHO Cells), was found to be safe and even more effective than BBIBP-CorV in eliciting humoral immune responses in BBIBP-CorV-primed individuals. Together, these results indicate that a third immunization schedule with either homologous or heterologous vaccine showed favorable safety profiles and restored potent SARS-CoV-2-specific immunity, providing support for further trials of booster vaccination in larger populations.


Subject(s)
Adolescent , Adult , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , China , Humans , Immunogenicity, Vaccine , Middle Aged , SARS-CoV-2 , Vaccination , Young Adult
7.
Protein & Cell ; (12): 90-101, 2022.
Article in English | WPRIM | ID: wpr-929171

ABSTRACT

The cyclic GMP-AMP (cGAMP) synthase (cGAS) has been identified as a cytosolic double stranded DNA sensor that plays a pivotal role in the type I interferon and inflammation responses via the STING-dependent signaling pathway. In the past several years, a growing body of evidence has revealed that cGAS is also localized in the nucleus where it is associated with distinct nuclear substructures such as nucleosomes, DNA replication forks, the double-stranded breaks, and centromeres, suggesting that cGAS may have other functions in addition to its role in DNA sensing. However, while the innate immune function of cGAS is well established, the non-canonical nuclear function of cGAS remains poorly understood. Here, we review our current understanding of the complex nature of nuclear cGAS and point to open questions on the novel roles and the mechanisms of action of this protein as a key regulator of cell nuclear function, beyond its well-established role in dsDNA sensing and innate immune response.


Subject(s)
Cell Nucleus/immunology , Humans , Immunity, Innate , Nucleotidyltransferases/immunology , Signal Transduction/immunology
8.
Article in English | WPRIM | ID: wpr-929019

ABSTRACT

OBJECTIVES@#Genetic mutation is one of the important causes for tumor genesis and development, but genetic mutation in nasopharyngeal carcinoma (NPC) has rarely been reported. This study explored the role of phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt), mammalian target of rapamycin (mTOR), and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway in the efficacy and prognosis in patients with NPC.@*METHODS@#A total of 31 patients with advanced NPC, who came from the Affiliated Cancer Hospital of Xiangya School of Medicine of Central South University/Hunan Provincial Cancer Hospital, were enrolled. All of the exons of 288 genes, introns of 38 genes and promoters or fusion breakpoint regions from the nasopharyngeal biopsy tissues before treatment were detected by the gene sequencing platform Illumina NextSeq CN500. The coding regions of 728 genes were carried out a high-depth sequencing of target region capture, and the 4 variant types of tumor genes (including point mutations, insertion deletions of small fragments, copy number variations, and currently known fusion genes) were detected. All of 31 patients received platinum-based induction chemotherapy combined with concurrent chemoradiotherapy and were followed up for a long time.@*RESULTS@#The 3-year regional failure-free survival (RFFS) and disease-free survival (DFS) in patients with PI3K-Akt pathway mutation were significantly lower than those in unmutated patients (χ2=6.647, P<0.05). The 3-year RFFS and DFS in patients with mTOR pathway mutations were significantly lower than those in unmutated patients, and there was significant difference (χ2=5.570, P<0.05). The rate of complete response (CR) in patients with unmutated AMPK pathway was significantly higher than that in patients with mutation at 3 months after treatment (P<0.05), and the 3-year RFFS and DFS in patients with AMPK pathway mutation were significantly lower than those in unmutated patients (χ2=4.553, P<0.05). PI3K-Akt/mTOR/AMPK signaling pathway mutations and pre-treatment EB virus DNA copy numbers were independent prognostic factors for 3-year RFFS and DFS in patients with NPC (both P<0.05).@*CONCLUSIONS@#The NPC patients with PI3K-Akt/mTOR/AMPK signaling pathway mutation have poor prognosis, and the detection of PI3K-Akt, mTOR, AMPK driver genes and signaling pathways by next-generation sequencing is expected to provide new idea for basic research and targeted therapy of NPC.


Subject(s)
AMP-Activated Protein Kinases/metabolism , DNA Copy Number Variations , Humans , Mutation , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Neoplasms/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Prognosis , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Sirolimus , TOR Serine-Threonine Kinases/metabolism
9.
Article in Chinese | WPRIM | ID: wpr-940801

ABSTRACT

ObjectiveTo investigate the efficacy of Bushen Shengxue prescription and Yiqi Yangxue prescription in the treatment of chronic aplastic anemia and the effect on T cell subsets and the expression of T-box expressed in T cells (T-bet) and GATA binding protein 3 (GATA3). MethodA total of 585 patients with chronic aplastic anemia who were treated in 19 hospitals in China from May 2018 to June 2021 were enrolled. With the prospective, double-blind and randomized control methods, the patients were randomized into three groups: kidney deficiency group, Qi and blood deficiency group, and control group. The three groups were respectively treated with Bushen Shengxue prescription granule, Yiqi Yangxue prescription granule, and Placebo (half the dose of Bushen Shengxue formula granules). In addition, all of them were given oral cyclosporin and androgen. The treatment lasted 6 months, with 3 months as a course. The blood routine indexes, T cell subsets, and fusion genes T-bet and GATA3 before and after treatment were analyzed, and the safety indexes were monitored. ResultDuring the observation, a total of 75 cases dropped out and 18 were rejected. Finally, 161 cases in the kidney deficiency group, 164 in the Qi and blood deficiency group, and 167 in the control group were included. After 6 months of treatment, the total effective rate was 98.8% (159/161) in the kidney deficiency group, which was higher than the 79.9% (131/164) in the Qi and blood deficiency group (χ2=30.135, P<0.01) and the 61.7% (103/167) in the control group (χ2=70.126, P<0.01). The total effective rate was higher in the Qi and blood deficiency group than in the control group (χ2=13.232, P<0.01). After treatment, the hemoglobin (HGB) content increased significantly in three groups (P<0.05) as compared with that before treatment, particularly the kidney deficiency group (P<0.01). After treatment, the white blood cell (WBC) count and platelet (PLT) count in the kidney deficiency group and the control group increased compared with those in the Qi and blood deficiency group (P<0.01). There was no specific difference in neutrophils (ANC) after treatment among the three groups. At the same time point, the level of T helper type 1 (Th1) cells, Th1/Th2 ratio (P<0.05), level of CD4+, and CD4+/CD8+ ratio (P<0.05) were significantly low in the kidney deficiency group among three groups. There was no significant difference in CD19-, HLA/DR+, and CD25+ between the kidney deficiency group and the other two groups, but the T-bet of the kidney deficiency group and the control group was lower than that of the Qi and blood deficiency group (P<0.05). ConclusionBushen Shengxue prescription exerts therapeutic effect on the aplastic anemia by improving the immunoregulatory mechanism, inhibiting the activity of immune system, modulating T cell subsets, suppressing Th1 and CD4+, and promoting bone marrow hematopoiesis. Moreover, it is safe with little side effects, which is worthy of further promotion.

10.
Article in Chinese | WPRIM | ID: wpr-940598

ABSTRACT

ObjectiveTo study the effect of Shenling Baizhusan on electrogastrogram in children with spleen deficiency diarrhea. To clarify the occurrence of gastric electrical rhythm disorder in children with this disease, and to study whether Shenling Baizhusan can improve the abnormal gastric motility in children with diarrhea (spleen deficiency) MethodA total of 125 children with spleen deficiency diarrhea in the outpatient department of Children's Hospital of Shanghai from October 2019 to March 2021 were selected as the research objects, and they were randomly divided into a control group (60 cases) and an observation group (65 cases). The children in the control group were treated with Montmorillonite powder combined with probiotics treatment, and the children in the observation group were additionally treated with Shenling Baizhusan. The course of treatment for both groups was 1 week. The clinical efficacy of the two groups of children after treatment and the scores of main traditional Chinese medcine(TCM) symptoms before and after treatment were compared, and the changes in the main parameters of electrogastrogram in children before and after treatment were compared. ResultAfter treatment, the total effective rate of observation group (90.77%, 59/65) was higher than that of control group (76.67%,46/60) (χ2=4.617, P<0.05). After treatment, scores of fecal morphology, frequency of defecation, fatigue, inappetence, and other symptoms in both groups were lower than that before treatment (P<0.05), and the observation group was lower than the control group (P<0.05). As compared with before treatment, the main frequency, the percentage of normal slow wave, and the percentage of normal gastric electrical rhythm in the two groups increased after treatment (P<0.05), and the control group was lower than the observation group (P<0.05). The proportion of children with slow gastric rhythm decreased (P<0.05) as compared with before treatment, and the control group was higher than the observation group (P<0.05). ConclusionShenling Baizhusan can significantly relieve the diarrhea symptoms in children with spleen deficiency diarrhea and improve gastric motility with good clinical effects.

11.
Article in Chinese | WPRIM | ID: wpr-940502

ABSTRACT

To give full play to the therapeutic advantages of traditional Chinese medicine (TCM) in sepsis, clarify the entry point of integrated TCM and western medicine, further standardize the clinical treatment of TCM, develop a recognized and integrated treatment protocol of TCM and western medicine, and improve the clinical efficacy on sepsis,the Chinese Association of Chinese Medicine organized TCM and western medicine experts specialized in sepsis treatment to conduct in-depth discussions on the advantages of TCM and integrated TCM and western medicine in the treatment of sepsis based on the TCM etiology and pathogenesis of sepsis, a representative acute and critical disease. They emphasized the pathogenesis characteristics of asthenia of healthy Qi and sthenia of pathogenic factors and summarized the roles of Chinese medicine in correcting the imbalance of inflammatory response, improving blood coagulation dysfunction, and relieving organ damage. Furthermore, they proposed the treatment protocol with integrated TCM and western medicine, which is expected to provide references for actual clinical treatment and scientific research.

12.
Chinese Journal of Hepatology ; (12): 443-446, 2022.
Article in Chinese | WPRIM | ID: wpr-935964

ABSTRACT

Artificial intelligence (AI) refers to the use of computer programs to simulate and extend human intelligence, and has application prospects in the diagnosis and treatment of diseases. This review focuses on the research status of the screening and diagnosis of NAFLD and nonalcoholic steatohepatitis using artificial intelligence technology, electronic health record data, multi-omics prediction models, image recognition technology based on liver imaging and pathological biopsy, and new drugs research and development, with a view to provide new ideas for the diagnosis and treatment.


Subject(s)
Artificial Intelligence , Biopsy/methods , Humans , Liver/pathology , Liver Cirrhosis/pathology , Liver Neoplasms/pathology , Non-alcoholic Fatty Liver Disease/pathology
13.
Article in Chinese | WPRIM | ID: wpr-935797

ABSTRACT

This paper reported a case of severe Chlamydia psittaci pneumonia. The patient had a clear history of contact with sick poultry. The clinical manifestations were dry cough, fever and respiratory failure. Chest CT showed consolidation in the lower lobe of the right lung, and a small amount of exudative ground-glass opacity in the left lung. Chlamydia psittaci was detected in bronchoalveolar lavage fluid (BALF) by metagenomic assay. After treatment with antibiotics such as nitroimidazoles and carbapenems, the patient was discharged with a better health condition.


Subject(s)
Bronchoalveolar Lavage Fluid , Chlamydophila psittaci , Humans , Metagenomics , Pneumonia , Psittacosis/drug therapy
14.
Chinese Journal of Pediatrics ; (12): 291-296, 2022.
Article in Chinese | WPRIM | ID: wpr-935689

ABSTRACT

Objective: To analyze the factors affecting the efficacy of mite subcutaneous immunotherapy (SCIT) in allergic asthma patients aged 5-18 years, and to find the best predictive model for the curative effect. Methods: The data of 688 patients aged 5-18 years with allergic asthma who completed more than 3 years of mite SCIT from December 2006 to November 2021 in the Department of Respiratory Medicine, Children's Hospital Affiliated to Nanjing Medical University were retrospectively analyzed. Male, results of skin prick test (SPT), age, daily medication score (DMS), visual analogue scale (VAS) score, and enrollment season were defined as independent variables. R language models, including Logistic regression model, random forest model and extreme gradient boosting (XGboost) model, were used to analyze the impact of these independent variables on the outcomes. The receiver operating characteristic curve was applied to compare the predictive ability of the models. Hypothesis testing of the area under curve (AUC) of the 3 models was performed using DeLong test. Results: There were 435 males and 253 females in the 688 patients. There were 349 patients aged 5-<8 years, 240 patients aged 8-<11 years, and 99 patients aged 11-18 years. SPT showed that 429 cases (62.4%) were only allergic to mite, and 259 cases (37.7%) were also allergic to other allergens. According to the efficacy after 3 years of SCIT, 351 cases (51.0%) discontinued the treatment and 337 cases (49.0%) required continued treatment. The DMS was 4 (3, 6) at initiation, 3 (2, 5) at 3 months, 3 (2, 5) at 4 months, 2 (1, 3) at 12 months, and 0 (0, 1) at 3 years of SCIT treatment. The VAS was 3.5 (2.5, 5.2) at initiation, 3.2 (2.2, 4.8) at 3 months, 2.6 (1.4, 4.1) at 4 months, 1.0 (0.6, 1.8) at 12 months, and 0.5 (0, 1.2) at 3 years of treatment. At 3, 4, and 12 months, the rate of decline in DMS was 0 (0, 20%), 16.7% (0, 33.3%), and 50.0% (31.0%, 75.0%), respectively; and the VAS decreased by 7.1% (3.2%,13.8%), 27.6% (16.7%,44.4%), and 70.2% (56.1%, 82.3%), respectively. Regarding the enrollment season, 99 cases were in spring, 230 cases in summer, 171 cases in autumn, and 188 cases in winter. The R language Logistic regression model found that DMS>3 points at 3 months (OR=-3.5, 95%CI:-4.3--2.7, P<0.01), male (OR=-1.7, 95%CI:-2.3--1.0), P<0.01), DMS decline rate>16.7% at 4 months (OR=-1.6, 95%CI:-2.3--0.8, P<0.01) and DMS decline rate>0 at 3 months (OR=-0.7, 95%CI:-1.3--0.2, P<0.05) had higher possibility of drug discontinuation; whereas, the decline rate of DMS at 12 months>50.0% (OR=0.7, 95%CI: 0.1-1.3, P<0.05), VAS at 12 months>1.0 points (OR=0.9, 95%CI: 0.3-1.6, P<0.05), and initial VAS<4.0 points (OR=1.0, 95%CI: 0.4-1.6, P<0.01) had lower possibility of drug discontinuation. Both the random forest model and the XGboost model showed that DMS>3 points at 3 months (mean decrease accuracy=30.9, importance=0.45) had the greatest impact on drug discontinuation. The AUC of the random forest model was the largest at 0.900, with an accuracy of 78.2% and a sensitivity of 84.5%. Logistic regression model had AUC of 0.891, accuracy of 80.0%, and sensitivity of 80.0%; XGboost model had AUC of 0.886, accuracy of 76.9%, and sensitivity of 84.5%. The AUC of the pairwise comparison model by DeLong test found that all three models could be used for the prediction of this data set (all P>0.05). Conclusions: The more drugs used to control the primary disease, and the more careful reduction of the control medicine after starting SCIT treatment, the more favorable it is to stop all drugs after 3 years. The random forest model is the best predictive model for the efficacy of mite SCIT in asthmatic children.


Subject(s)
Adolescent , Allergens , Animals , Asthma/therapy , Child , Child, Preschool , Desensitization, Immunologic/methods , Female , Humans , Immunotherapy/methods , Injections, Subcutaneous , Male , Mites , Retrospective Studies
15.
Chinese Journal of Pediatrics ; (12): 227-231, 2022.
Article in Chinese | WPRIM | ID: wpr-935675

ABSTRACT

Objective: To investigate the clinical features, pathological phenotype, treatment and prognosis of Castleman's disease in children. Methods: Clinical data of 15 children diagnosed with Castleman's disease in Henan Provincial People's Hospital and the First Affiliated Hospital of Zhengzhou University from May 2010 to October 2019 were analyzed retrospectively. The clinical characteristics, laboratory examination and histopathological data were analyzed. Results: Among the 15 Castleman's disease patients, 12 were males and 3 females. The age of first visit was 12 (10, 15) years. The time from mass discovery to pathologic diagnosis was 9.0 (2.0, 13.0) months. The majority of patients were unicentric (13 cases), and the histopathological type was hyaline vascular (11 cases). Unicentric lesions were most common in the neck (11 cases), all 13 patients received complete surgical resection of the lesions, the follow-up time was 20.0 (13.5, 50.5) months, and the prognosis was good. Two cases were multicentric type, the pathological types were mixed variant, meeting the criteria of idiopathic Castleman's disease, the two children underwent partial surgical resection, one was treated with rituximab and prednisone and the other was treated with thalidomide and prednisone. The follow-up time was 32 months and 10 month, both of them had good prognosis. Conclusions: Most cases of Castleman's disease in children are diagnosed late, and the unicentric type is dominant. The most common pathological type is hyaline vascular, which is characterized by painless lymphadenopathy, while multicentric type has systemic symptoms and both of them have a good overall prognosis.


Subject(s)
Castleman Disease/therapy , Female , Humans , Male , Neck/pathology , Prognosis , Retrospective Studies , Rituximab
16.
Chinese Journal of Pediatrics ; (12): 203-208, 2022.
Article in Chinese | WPRIM | ID: wpr-935671

ABSTRACT

Objective: To analyze the eligibility of empirical antibiotic therapy in culture positive sepsis in the pediatric intensive care unit (PICU), and to explore the application of antibiotic de-escalation (ADE) in children with sepsis and its impact on prognosis. Methods: A total of 123 children with sepsis-associated organ dysfunction or septic shock admitted to the PICU of Shengjing Hospital of China Medical University from January 2018 to December 2020 were retrospectively analyzed. The general information, laboratory tests, the use of empirical anti-bacterial drugs and the application of ADE were collected. According to the adjustment of anti-bacterial drugs, these children were divided into ADE group and non-ADE group. Comparisons between groups were performed with unpaired Student t test, or Mann-Whitney U test, or chi-square test or Fisher exact test. Results: In these 123 children, 70 were males and 53 were females, the age was 11.4 (2.8, 56.5) months. Body fluid culture was detected positive in 41 children including 3 children (7.3%) who received inadequate empirical antibiotic therapy and 38 children (92.7%) who received adequate empirical antibiotic therapy. Excluding 10 children who received appropriate therapy, 28 received unnecessary broad-spectrum antibiotics. There were no significant differences regarding the PICU all-cause mortality rates, length of PICU stay, hospitalization cost, duration of mechanical ventilation, as well as incidences of re-infection between the ADE group (n=46) and non-ADE group (n=77) (all P>0.05). However, among the 101 children who have used antibiotics against multidrug-resistant organism, the duration of such antibiotics use in ADE group (n=43) was shorter than that in non-ADE group (n=58) (5.0 (4.0, 12.0) vs. 9.5 (7.0, 13.0) d, Z=-3.14, P=0.002). Conclusions: Overuse of unnecessary broad-spectrum empirical antibiotics is very common, but the application of ADE is rather disappointing. ADE can reduce the use of anti-bacterial drugs against multi-drug resistant bacteria without significant adverse effects on prognosis in children with sepsis.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Child , Female , Humans , Infant , Male , Prognosis , Retrospective Studies , Sepsis/drug therapy , Shock, Septic
17.
Chinese Journal of Pediatrics ; (12): 108-113, 2022.
Article in Chinese | WPRIM | ID: wpr-935652

ABSTRACT

Objective: To investigate the clinical features, survival and prognostic risk factors of children with hepatoblastoma (HB). Methods: Clinical data of 83 children with newly treated HB at the Department of Hematology and Oncology, Children's Hospital, the First Affiliated Hospital of Zhengzhou University from January 2012 to October 2019 were analyzed retrospectively. The sex, age, first clinical manifestations, pretreatment extent of disease (PRETEXT) stages, pathological types, initial alpha-fetoprotein (AFP), treatment methods and treatment outcome of all patients were summarized. The children diagnosed before 2018 were treated with "Wuhan Protocol", and those who diagnosed after 2018 were treated with the "Expert Consensus for Multidisciplinary Management of Hepatoblastoma"(CCCG-HB-2016) protocol. Kaplan-Meier survival analysis was used to calculate the survival rate, Log-Rank test was used in univariate analysis, and the Cox regression model was used in multivariate prognosis analysis. Results: Among 83 cases, there were 51 males and 32 females. The age of onset was 25.2 (9.0, 34.0) months old, and 64 cases (77%) were under 3 years old. The most common first clinical manifestation was abdominal mass in 45 cases (54%). There were 8 cases of PRETEXT stage Ⅰ, 43 cases of stage Ⅱ, 20 cases of stage Ⅲ and 12 cases of stage Ⅳ. During the follow-up period of 40 (17, 63) months, the 1-year overall survival (OS) rate and event-free survival (EFS) rate were (84±4) % and (79±5) %, respectively, and 5-year OS rate and EFS rate were (78±5) % and (76±5) %, respectively. Fifty-five cases were treated with "Wuhan Protocol", and the 5-year OS and EFS rate were (73±6) % and (71±6) %, respectively. Twenty-eight cases were treated with CCCG-HB-2016 protocol, and the 5-year OS and EFS rate were (88±7) % and (82±9) %, respectively. Multivariate COX regression analysis showed that AFP did not turn negative after 3 courses of postoperative chemotherapy (HR=9.228, 95%CI 1.017-83.692) and PRETEXT stage Ⅳ (HR=6.587, 95%CI 1.687-25.723) were independent risk factors affecting the prognosis of children with HB. Conclusions: The "Wuhan Protocol" and CCCG-HB-2016 protocol were effective in the treatment of children with HB. AFP did not turn negative after 3 courses of postoperative chemotherapy and PRETEXT stage Ⅳ were independent risk factors affecting the prognosis of children with HB.


Subject(s)
Female , Hepatoblastoma/drug therapy , Humans , Infant , Liver Neoplasms , Male , Prognosis , Retrospective Studies , Treatment Outcome
18.
Chinese Journal of Pediatrics ; (12): 56-61, 2022.
Article in Chinese | WPRIM | ID: wpr-935640

ABSTRACT

Objective: To investigate the clinical features, diagnosis,treatment and prognosis of children with acute lymphoblastic leukemia complicated with mucormycosis, and to improve the understanding of the disease. Methods: The clinical data of 3 children with acute lymphoblastic leukemia (ALL) complicated with mucormycosis treated at the First Affiliated Hospital of Zhengzhou University between October 2020 and January 2021 were analyzed retrospectively. Literature search and review covered the China national knowledge infrastructure, Wanfang database and Pubmed using the keywords of "acute lymphoblastic leukemia" and "mucormycosis" up to June 2021. Results: Case 1, a 12-year-old boy, was diagnosed with ALL, developed fever and chest pain during induction therapy. The Metagenomic next-generation sequencing (mNGS) testing of alveolar perfusion fluid suggested infection with Rhizopus oryzae. Amphotericin B combined with posaconazole was applied and amphotericin B was removed after improvement. Bone destruction was indicated by CT. Amphotericin B was applied again. Case 2, a 4-year-old boy, with a history of pallor and tetter, was diagnosed with ALL. He developed cough and fever during induction therapy. mNGS of blood suggested infection with Rhizomucor pusillus. Amphotericin B combined with voriconazole was applied, but the situation was not significantly improved. The disseminated infection occurred. Amphotericin B combined with posaconazole was applied and vacuum sealing drainage was performed. Case 3, a 2-year-old girl, was diagnosed with ALL, developed fever and cough during induction therapy. Rhizomucor pusillus was indicated by mNGS. Amphotericin B combined with posaconazole was used, and posaconazole was stopped after improvement. Follow-up until June 2021, the condition of the 3 children improved. There was no recurrent Mucor infection, and the primary hematopathy was in complete remission. According to the literature, 7 reports were found in Chinese journals, while 17 reports were found in English literature, 25 cases have been reported. Among a total of 28 children, 11 cases rhino-orbito-cerebral mucormycosis, four pulmonary mucormycosis, 2 cutaneous mucormycosis, 2 gastrointestinal mucormycosis and 9 disseminated mucormycosis. There were 17 cases developed infection during induction chemotherapy, 8 cases during maintenance therapy, 3 cases after hematopoietic stem cell transplantation. Voriconazole was used in 15 cases; 19 cases were treated with combined surgery, 7 cases were treated with drugs only, 2 cases were untreated; 21 cases showed improvement after treatment. Death occurred in seven cases. Conclusions: ALL complicated with mucormycosis often occurs in the stage of induction therapy. The clinical features lacked specificity, mNGS can help find the pathogen and provide evidence for diagnosis. Surgical treatment also could be combined when necessary, which is helpful to improve the prognosis.


Subject(s)
Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Child , Child, Preschool , Female , Humans , Male , Mucormycosis/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Retrospective Studies
19.
Chinese Journal of Surgery ; (12): 79-83, 2022.
Article in Chinese | WPRIM | ID: wpr-935583

ABSTRACT

Objective: To compare the effects of preoperative neoadjuvant chemotherapy and postoperative adjuvant chemotherapy on the long-term survival of patients with radical resection for esophageal squamous cell carcinoma. Methods: Totally 1 082 patients with stage T3-4aN0-3M0 thoracic esophageal squamous cell carcinoma were recruited in this study who underwent radical resection at Department of Thoracic Surgery, Fourth Hospital, Hebei Medical University from January 2005 to January 2015. There were 798 males and 284 females, with a median age of 61 years (range: 37 to 86 years). There were 138 patients undergoing preoperative neoadjuvant chemotherapy, 392 patients postoperative adjuvant chemotherapy, and 552 patients surgery alone. The neoadjuvant chemotherapy group was used as the benchmark group to match the propensity score with the adjuvant chemotherapy group and the surgery-only group respectively at a ratio of 1∶3. A total of 7 covariates including tumor location, number of positive lymph nodes, tumor invasion depth, tumor differentiation degree, surgical procedure, vascular tumor thrombus and nerve invasion were included, and the caliper value was taken as 0.1. After matching, a total of 699 patients were included for the analysis, including 128 patients in the neoadjuvant chemotherapy group, 267 patients in the adjuvant chemotherapy group, and 304 patients in the surgery alone group. The Kaplan-Meier method was used to generate the survival curves which was tested by the Log-rank method for survival analysis. Results: After matching analysis, the 5-year overall survival rate was 41.5% in the neoadjuvant chemotherapy group with a median overall survival time of 43 months (95%CI: 27 to 59 months), 57.6% in the adjuvant chemotherapy group with a median overall survival time unreached, and 24.9% in the surgery alone group with a median overall survival time of 28 months (95%CI: 25 to 31 months) (χ²=60.475, P<0.01). For overall survival after matching, the adjuvant chemotherapy group was better than the neoadjuvant chemotherapy group (χ²=11.384, P=0.001), the neoadjuvant chemotherapy group was better than the surgery alone group (χ²=8.654, P=0.003), and the adjuvant chemotherapy group was better than surgery alone group (χ²=60.234, P<0.01). Conclusion: Both preoperative neoadjuvant chemotherapy and postoperative adjuvant chemotherapy can improve the long-term survival of patients with locally advanced esophageal squamous cell carcinoma undergoing radical resection, and the improvement effect of postoperative adjuvant chemotherapy is more obvious.


Subject(s)
Adult , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Prognosis , Propensity Score , Retrospective Studies , Survival Rate
20.
Chinese Journal of Pathology ; (12): 407-412, 2022.
Article in Chinese | WPRIM | ID: wpr-935554

ABSTRACT

Objective: To investigate immunohistochemical patterns of CXorf67 and H3K27me3 proteins in central nervous system germ cell tumors (GCTs) and to assess their values in both diagnosis and differential diagnosis. Methods: A total of 370 cases of central nervous system GCTs were collected from 2013 to 2020 at Huashan Hospital of Fudan University, Shanghai, China. The expression of CXorf67, H3K27me3 and commonly-used GCT markers including OCT4, PLAP, CD117, D2-40, and CD30 by immunohistochemistry (EnVision method) was examined in different subtypes of central nervous system GCTs. The sensitivity and specificity of each marker were compared by contingency table and area under receiver operating characteristic (ROC) curve. Results: Of the 370 cases there were 282 males and 88 females with a mean age of 19 years and a median age of 17 years (range, 2-57 years). Among the GCTs with germinoma, the proportions of male patients and the patients with GCT located in sellar region were both higher than those of GCTs without germinoma (P<0.05), respectively. CXorf67 was present in the nuclei of germinoma and normal germ cells, but not in other subtypes of GCT. H3K27me3 was negative in germinoma, but positive in the nuclei of surrounding normal cells and GCTs other than germinoma. In the 283 GCTs with germinoma components, the expression rate of CXorf67 was 90.5% (256/283), but no cases were positive for H3K27me3. There was also an inverse correlation between them (r2=-0.831, P<0.01). The expression rates of PLAP, OCT4, CD117 and D2-40 were 81.2% (231/283), 89.4% (253/283), 73.9% (209/283) and 88.3% (250/283), respectively. In 63 mixed GCTs with germinoma components, the expression rate of CXorf67 was 84.1% (53/63), while all cases were negative for H3K27me3. The expression rates of PLAP, OCT4, CD117 and D2-40 were 79.4% (50/63), 79.4% (50/63), 66.7% (42/63) and 87.3% (55/63), respectively. The 6 markers with largest area under ROC curve in ranking order were H3K27me3, CXorf67, D2-40, OCT4, PLAP and CD117 (P<0.05). Conclusions: CXorf67 and H3K27me3 have high sensitivity and high specificity in diagnosing germinoma. There is a significant inverse correlation between them. Therefore, they can both be used as new specific immunohistochemical markers for the diagnosis of GCTs.


Subject(s)
Adolescent , Adult , Brain Neoplasms/pathology , Central Nervous System/pathology , Central Nervous System Neoplasms/metabolism , Child , Child, Preschool , China , Female , Germinoma/pathology , Histones , Humans , Male , Middle Aged , Neoplasms, Germ Cell and Embryonal/diagnosis , Oncogene Proteins , Transcription Factors/metabolism , Young Adult
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